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Table of Contents
ORIGINAL ARTICLE
Year : 2019  |  Volume : 10  |  Issue : 4  |  Page : 184-189

Clinicodemographic profiling of zika outbreak in Jaipur, Rajasthan


1 Department of Medicine, SMS Medical College, Jaipur, Rajasthan, India
2 Directorate Medical and Health Services, Integrated Disease Surveillance Project, Government of Rajasthan, Jaipur, Rajasthan, India
3 Department of Microbiology, SMS Medical College, Jaipur, Rajasthan, India

Date of Submission15-Jun-2019
Date of Decision23-Jun-2019
Date of Acceptance23-Jun-2019
Date of Web Publication18-Nov-2019

Correspondence Address:
Dr. Mayank Gupta
Hardik Medicos, S-81, Barkat Nagar Chouraha, Tonk Phatak, Jaipur - 302 015, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/INJMS.INJMS_65_19

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  Abstract 


Background: The 2018 postmonsoon outbreak of Zika virus infection, in a localized pocket of city of Jaipur, Rajasthan, so far the largest in India, alarmed the health authorities to optimize surveillance and measures. Hence, a community-based study to analyze the clinicodemographic profile was conducted to gain better understanding of its squeal. This study aimed to analyze the clinicodemographic profile of this new entrant viral infection. Methods: The study was designed as a community-based observational study. 1,488,870 people in vicinity of the index case were surveyed clinically from October to November 2018. A total of 1925 febrile individuals including pregnant ones in various trimesters of their pregnancy were screened for Zika infection by reverse-transcriptase-polymerase-chain-reaction (RT-PCR). Among these, 153 were RT-PCR positive and 111 cases consenting for the study were included and data collected were analyzed using SPSS 16 software. Results: The mean age of the study population was 27.51 years (95% confidence interval = 24.78–30.25), 53% of the patients were females. Out of 59 Zika-positive females, 27 (46%) were pregnant; 12 (44.4%) were in first trimester and 9 (33%) and 6 (22.2%) in second and third trimester, respectively. The incubation period ranged from 2 to 10 days, the most common symptom being low grade fever in 82%, followed by myalgia in 64.9% and arthralgia in rheumatoid distribution in 55.9%. On examination, a widely distributed blanching maculopapular rash was seen in 28.8%; nonpurulent conjunctivitis differentiating it from dengue was seen in 16.2%. Conclusions: Although Zika, a commonly prevalent virus in dengue endemic belts, yet unknown to our territory, usually causes a mild febrile illness, it can be a cause of intense apprehension to many if infection occurs in the first trimester of pregnancy. Formulating guidelines to tackle Zika pregnancy is a daunting task and needs collaboration across the globe to carry out future research and to get the knowhow.

Keywords: Clinicodemographic, maculopapular rash, pregnancy, Zika virus disease


How to cite this article:
Sharma R, Agarwal M, Gupta M, Singh R, Mahavar SK, Sharma R, Meena D. Clinicodemographic profiling of zika outbreak in Jaipur, Rajasthan. Indian J Med Spec 2019;10:184-9

How to cite this URL:
Sharma R, Agarwal M, Gupta M, Singh R, Mahavar SK, Sharma R, Meena D. Clinicodemographic profiling of zika outbreak in Jaipur, Rajasthan. Indian J Med Spec [serial online] 2019 [cited 2019 Dec 14];10:184-9. Available from: http://www.ijms.in/text.asp?2019/10/4/184/271224




  Introduction Top


Zika virus is a mosquito-borne ss-RNA flavivirus, related closely to yellow fever, Chikungunya, and West Nile fever virus, predominantly prevalent in dengue endemic areas of Central America, most of South America, sub-Saharan Africa, and South East Asia.[1] It was an alarming situation when it entered the city of Jaipur, Rajasthan, India in the postmonsoon months when an index case, which was an 85-year-old female, was picked up during surveillance scanning. Ministry of Health and Family Welfare, Government of India, reported 153 positive laboratory confirmed cases of Zika virus from Jaipur, Rajasthan on November 16, 2018 which was the largest outbreak so far in the country [Figure 1]. According to the World Health Organization (WHO) Zika virus classification scheme, India was placed under category 2, suggesting ongoing transmission of the virus, with first outbreak in Gujarat and second in Tamil Nadu reporting three and two cases, respectively, in 2017;[2] subsequently, Bhopal reported 130 laboratory confirmed Zika-positive cases in October 2018.
Figure 1: India has Asia's most Zika-exposed population. Largest outbreak till date being reported from Jaipur, Rajasthan

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Since its first isolation in 1947, from blood of febrile sentinel rhesus macaque, from Zika forest of Uganda, the virus remained obscured for almost seven decades with occasional sporadic outbreaks confined to South East Asia and Africa.[3] Urbanization and globalization broke the barriers and led to the spread of Zika virus beyond small remote geographic areas and the world saw three major outbreaks in just a decade, 2007 (Yap islands, Federated states of Micronesia);[4] 2013–2014 (French Polynesia);[5] and May 2015 (Brazil, South America). The Brazil outbreak, first in the Americas, created a global alarm when ~4,44,000–13,00,000 people were infected and 4,300 cases of microcephaly[6] were reported, and led WHO to declare this as a Public Health Emergency of International Concern on February 1, 2016.[7]

Zika virus infection is usually characterized by mild self-limiting illness, and has variably been linked to congenital birth defect, particularly microcephaly[8] and neurological complication like Guillain–Barré syndrome (GBS).[9] Since there is no specific antiviral treatment or vaccine available, primary focus should be prevention, especially in the pregnant individuals. Despite growing knowledge about the virus, paucity in understanding the domain of virus's vector, reservoir, pathogenesis, genetic diversity, and potential synergistic effects of coinfection with other circulating agents remain. These questions highlight the need for global risk assessment and research to optimize surveillance and preparedness to combat emerging and re-emerging epidemics of Zika. The aim of this study is to highlight the clinicodemographical features of the current outbreak of Zika, to share data to aid regulatory policies for curtailing future outbreaks by developing a better understanding of the virus.


  Methods Top


The present study, a community-based observational study, was designed to profile the Zika virus outbreak. The domain was a localized geographic pocket of 3-km radius, the epicenter of Zika activity. The study was conducted over a period of 56 days from September 22, 2018–November 16, 2018 after approval by the Ethics Committee of Sawai Man Singh (S. M. S.) Medical College and attached hospitals, Jaipur, Rajasthan, India. Index case was identified in Jaipur during implementation of surveillance guidelines issued by central laboratory agencies of India for the detection of this infection in dengue-affected belts. 8615 teams of paramedics and medical officers were deployed to screen 300,268 houses, in which 1,488,870 people were surveyed and 12,701 febrile cases including 3823 pregnant individuals were identified. Among them, 731 cases with clinical features consistent with Zika virus disease (ZVD), 1081 pregnant women, and 113 random contacts were tested. Their serum and urine samples were tested by real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) at Advanced Virology Research Lab, S. M. S. Medical College and Hospital. Of the 153 cases that tested positive for Zika infection, 111 were included into the study. Detailed history regarding age, sex, duration of illness, various symptoms, associated comorbidities, pregnancy, duration of pregnancy, and complications were noted for those included in the study. The data, thus collected, were statistically analyzed using SPSS 16 software (International Business Machines Corporation (IBM), Armonk, New York, US). The teams deployed checked out the various breeding sites and containers for vector, Aedes aegypti to reduce the source of vector-borne transmission and curtail the spread.


  Results Top


Amongst a total of 1925 cases screened, 153 cases (7.9%) including 27 (2.5%) pregnant individuals were positive for Zika virus infection. Of the 111 laboratory-confirmed positive cases enrolled in the study, 59 (53%) were females and 52 (47%) were males. The mean age was 27.5 ± 14.5 years (range 4–90 years) (95% confidence interval [CI] = 24.78–30.25); 96 (86%) were ≤40 years of age, further grouping showed that 47 (42%) and 39 (35%) were in the age groups 21–30 years and 11–20 years, respectively [Table 1].
Table 1: Age distribution of cases

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The average incubation period of Zika virus infection was 4.9 days (95% CI = 4.59–5.21), and median incubation period was 6 days ranging from 2 to 10 days [Figure 2]. Of 59 positive females, 27 (46%) were pregnant and 32 (54%) were nonpregnant. The average age of pregnant patients in the series was 24 ± 3.3 years (range 18–29 years) and all were symptomatic. Among the pregnant patients, most patients 12 (44.4%) were in first trimester, 9 (33.3%), and 6 (22.2%) in second and third trimester, respectively, with mean age of 24.8 ± 3.6, 23.3 ± 2.8 and 23.2 ± 3.7, respectively, in the three trimesters. None of the pregnant women on screening by ultrasound had any fetal congenital anomalies. None of the cases had any underlying co-morbidity.
Figure 2: Cases of Zika virus disease outbreak in Jaipur city between October and November 2018

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There were 10 (9%) asymptomatic cases of 111 cases and 91% were symptomatic. The symptomatology observed is tabulated in [Table 2]. The most common symptom observed was fever which was recorded in 82% cases, followed by myalgia (64.9%), self-limiting arthralgia involving joints in rheumatoid distribution (55.9%), malaise (44.1%), and headache (38.7%). Fever was low grade in most of the cases (<100°F). On examination, blanching maculopapular rash involving face, trunk, extremities, and palms and soles was seen in 28.8% which was pruritic in 21.6%, followed by nonpurulent conjunctivitis present in 16.2%, differentiating it clinically from dengue. Other symptoms such as retro-orbital pain were reported in 14.4% and gastrointestinal symptoms such as nonspecific abdominal pain and vomiting were seen in 9.9% and 6.3%, respectively. There was one case (0.9%) each of cervical lymphadenopathy and petechial hemorrhage in the study group. None had any neurological manifestation in the form of seizures, altered sensorium, or GBS.
Table 2: Profiling of symptomatology of current Zika outbreak

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  Discussion Top


Zika virus remained obscured for almost seven decades since its discovery in 1947; but, in last one decade, several large outbreaks apart from Africa and South East Asia, along with its association with congenital birth defects and worrisome neurological sequel such as GBS have periodically put the health organizations on an alarming foot.

Zika has two modes of transmission one is vector borne and other is nonvector borne including congenital,[10] perinatal,[11] and sexual transmission.[12] In our study, all the cases were of vector-borne transmission, following bite of A. aegypti mosquito.

The incubation period of Zika from mosquito bite to symptom onset is not well established and is ~2–14 days as in other flaviviridae infections.[13] In our study, the incubation period too ranged from 2 to 10 days. Demographic profiling of the 111 RT-PCR-proven positive cases enrolled in the study revealed that Zika infection predominantly affected females (53%) as compared to 42% males. The mean age of infection in our study was 27.5 years with maximum number of infected in the study belonging to age group ≤40 years (86%). These results were similar to those of Lozier et al. from Puerto Rico; wherein too, the maximum cases were of females and individuals ≤40 years age. However, neither female sex nor younger age was associated with increased Zika virus incidence or prevalence.[14]

A total of 1,081 pregnant women were tested, of which 27 (2.5%) tested positive for Zika virus by RT-PCR in our series with 44.4% in the first trimester of pregnancy, followed by second trimester (33.3%) and third trimester (22.2%). The average age of pregnant women in the study was 24 years (18–29 years). All the pregnant women positive for Zika virus in the series were symptomatic, but none on screening by prenatal ultrasound had fetal congenital anomaly during this limited period. In a serial follow-up by Flamand et al., from French Guiana,[15] 2016, 3,050 pregnant individuals, aged 14–48 years, were screened by RT-PCR, and 573 (19%) had laboratory confirmed ZVD and 141 (24.6%) of them were in first trimester of pregnancy.

Majority of the clinical manifestations of Zika virus are mild and self-limiting, severe disease requiring hospitalization is rare, and the case fatality rates are low. In the present study, most of the cases were symptomatic (91%) with fever (37.4°C–38°C) being the most common presenting symptom (82%), followed by myalgia (64.9%), arthralgia (55.9%), malaise (44.1%), and headache (38.7%). It is akin to the study by Jimenez Corona et al.,[16] who analyzed 93 autochthonous cases of Zika in Mexico; wherein too, the predominant symptom was fever (96.6%), followed by rash (93.3%), nonpurulent conjunctivitis (88.8%), headache (85.4%), and myalgia (84.3%). This was in contrast to the study reported from Rio de Janeiro, Brazil,[17] based on a large number of suspected and laboratory-confirmed cases of Zika; the most common symptom was macular or maculopapular rash (97%), followed by pruritis (79%), prostration (73%), headache (66%), arthralgia (63%), myalgia (61%), and nonpurulent conjunctivitis (56%).

The distinguishing features of Zika virus which differentiate it from other flaviviruses, like blanching maculopapular rash over palms and soles, pruritis, and nonpurulent conjunctivitis in this series was found in 28.8%, 21.6%, and 16.2% cases, respectively. One case each of lymphadenopathy involving cervical lymph nodes and bleeding manifestation in the form of petechiae were seen in our series. Similarly, unusual manifestations such as lymphadenopathy, hematoma, and hematospermia have been described in patients with Zika infection in some reports.[12]

After ultrasonographic screening, no cases of congenital birth defects such as microcephaly, placental calcification, or other anomalies were reported in fetus of infected pregnant females. Greatest risk of microcephaly is in the first trimester, and it is estimated to be 0.88% when we assumed an 80% overall ZIKV infection rate and 100% over-reporting of microcephaly cases, and to 13.2%, when we assumed a 10% ZIKV infection rate and no over-reporting.[18] Thus the risk of microcephaly varies directly with the rate of infection and is uncertain. A plausible neuropathologic link between Zika virus and central nervous system anomalies is supported by a research showing viral neurotropism in intraperitoneally infected mice.[3] Brasil et al. published preliminary results of 88 pregnant women. Among the 72 women with confirmed Zika infection, fetal abnormalities were observed in 12 (29%); none of the 16 women with negative tests had fetal abnormalities.[19]

In case reports of microcephaly, documented maternal Zika virus infection most often occurred between 7 and 13 weeks of gestation; but in some cases, it occurred as late as 18 weeks of gestation.[20] Thus, pregnant women in the first trimester of their pregnancy with laboratory confirmed Zika infection must undergo screening prenatal ultrasound every 3–4 weeks, and the infant should be tested at birth.[21]

No case of GBS was reported in our series of 111 cases as was previously reported from outbreaks of Pacific (French Polynesia, 2013–2014; wherein 38 cases were reported among an estimated 28,000 persons who sought medical care) and Americas.[22] A temporal and geographic relationship has been observed between GBS and Zika virus outbreaks in the Pacific and the Americas. However, a direct causal relationship has not yet been definitively established.[9]

Clinical evaluation alone is unreliable for diagnosis of Zika virus infection because of clinical overlap and concurrently circulating arboviral infections. Thus, diagnosis relies on laboratory testing by RT-PCR and not on the serological tests, due to the challenge arising from the “original antigenic sin” phenomenon,[23] i.e., serologic cross reactivity, for patients who have previously been exposed to a heterologous flavivirus by natural infection or vaccination; in such cases, the antibody response to the previous infecting flavivirus will be more vigorous than the response to the current one. This is particularly problematic in areas in which dengue is endemic; where >90% of the population may have had previous exposure to dengue virus and these two may be co-circulating.[24]

National guidelines are being implemented for extensive surveillance, detection of Zika virus infection especially in pregnant women, vector control measures, and public health awareness. Global trade and travel are closely monitored for imminent Zika transmission to neighboring countries. Nonessential travel to affected areas should be deferred or delayed. Personal protective measures such as use of mosquito repellants and wearing light-colored clothes covering full body parts to avert mosquito bites should be implemented. WHO issues timely advisory alerts for pregnant individuals. Pregnant women should avoid or consider postponing travel to areas below 6500 feet (2000 meters) where mosquito transmission of Zika virus is ongoing.[25]


  Conclusions Top


WHO pointed out in 2016 that any country in the dengue belt that has the A. aegypti mosquito, the vector for both dengue and the Zika virus, should be on watch out for resurgence of ZVD.[26] This became true in 2018, when Rajasthan, India encountered ZVD in a limited pocket of our city Jaipur with a population of 3.1 million. The limitation of key importance is the nonavailability of a specific serological test for Zika virus. The available serological test is limited by cross-reactivity, and this is important as the RT-PCR assay in serum and urine can detect the infection only up to 7–14 days. Although Zika is a minor self-limiting illness, it sometimes may have grave implications if infection occurs during pregnancy; thus, the main focus should be to screen febrile pregnant patients. We lack guidelines to tackle Zika-positive pregnancy and to formulate such guidelines remains a daunting task. Further research to follow up infected pregnant women in various trimesters from this contemporary outbreak with follow-up of their newborns will improve our understanding of congenital anomalies associated with Zika and its actual incidence. Furthermore, whether congenital Zika syndrome/GBS has any association with specific genotype shall remain a matter of future research. A lack of antiviral or preventive vaccine makes it prudent to implement effective preventive measures such as vector control, personal protective measures against mosquito bite, and avoiding travel to mosquito transmission areas, especially by pregnant women as well as abstaining from unprotected sex with infected partner for at least 3 months from symptom onset to prevent sexual transmission. According to WHO fact sheet on vector-borne diseases, more than half of the world's population resides under constant threat of deadliest vectors, the mosquitoes, claiming millions of lives every year from mosquito-borne diseases such as Dengue, Chikungunya, Zika, West Nile virus, Yellow fever virus, and Malaria. Thus, sustained mosquito control efforts are important to prevent these outbreaks.

Acknowledgment

The sudden rise in ZVD cases led to formation by the State Government of Rajasthan of a very proactive task force to intimidate it. This was under the dynamic stewardship of Mrs. Veenu Gupta the Additional Chief Secretary Government of Rajasthan, Department of Medical and Health, who along with Dr. V K Mathur Director, Dr. Ravi Prakash Mathur, Additional Director Medical Health Services of Rajasthan and others worked painstakingly. This task force was instrumental in countering the challenges of this abrupt anomalous strike. The authors thankfully acknowledge their guidance, encouragement, and support for this work.

Financial support and sponsorship

None.

Conflicts of interest

There are no conflicts of interest.



 
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